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Oral Montelukast, Inhaled Beclomethasone, and Placebo for Chronic Asthma: A Randomized, Controlled Trial

Kerstin Malmstrom, PhD; Guillermo Rodriguez-Gomez, MD; Jeremias Guerra, MD; Cesar Villaran, MD; Andres Piñeiro, MD; Lynn X. Wei, PhD; Beth C. Seidenberg, MD; Theodore F. Reiss, MD, for the Montelukast/Beclomethasone Study Group*
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From Merck Research Laboratories, Rahway, New Jersey; Instituto Costarricense de Investigaciones Clinicas, San Jose, Costa Rica; Social Security General Hospital, Guatemala City, Guatemala; and Clinica Ricardo Palma, Lima, Peru.

Ann Intern Med. 1999;130(6):487-495. doi:10.7326/0003-4819-130-6-199903160-00005
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Background: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.

Objective: To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.

Design: Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.

Setting: 36 sites worldwide.

Patients: 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.

Interventions: Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 µg twice daily, administered with a spacer device; or placebo.

Measurements: Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed β-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.

Results: Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was −0.62 for beclomethasone, −0.41 for montelukast, and −0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.

Conclusions: Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.

*For a listing of members of the Montelukast/Beclomethasone Study Group, see the Appendix.


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Figure 1.
Trial profile.1

A total of 2253 patients were screened, and 895 were randomly assigned to study groups. The most common reason for exclusion was failure to meet the FEV criteria (40% of excluded patients were excluded for this reason).

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Figure 2.
Mean percentage change from baseline (SE) in FEV 1 over the 12-week treatment period.nn

± Black circles represent patients receiving montelukast, 10 mg once daily; black triangles represent patients receiving inhaled beclomethasone, 200 µg twice daily; and squares represent patients receiving placebo. The dotted lines represent the treatment effect for the subsets of patients switched from active treatment to placebo (according to the initial allocation schedule) during the washout period. White circles represent patients switched from montelukast to placebo ( = 52); white triangles represent patients switched from beclomethasone to placebo ( = 43).

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Figure 3.
Distribution of treatment responses for FEV 1 .1

The response distributions are shown as histograms for predefined intervals of percentage change in FEV . Striped bars represent patients receiving montelukast, 10 mg once daily; white bars represent patients receiving inhaled beclomethasone, 200 µg twice daily.

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Figure 4.
Onset of action of montelukast, beclomethasone, and placebo.PEFR

Treatment effect for peak expiratory flow rate ( ) in the morning over the first 21 days of treatment. Vertical lines represent SEs.

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Figure 5.
Time to first asthma attack.PPP

The proportion of patients without an asthma attack was estimated by using a Kaplan-Meier plot. = 0.006 for montelukast compared with placebo; = 0.001 for beclomethasone compared with placebo; and = 0.129 for montelukast compared with beclomethasone.

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